Dual-targeting VEGFR1 and PD-L1 CAR-T for Cancers Patients With Pleural or Peritoneal Metastases

NCT05477927 | Unknown Phase 1

• 1 other identifier: MCART-006
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

Serosal cavity metastases of malignant tumor seriously affects the quality of life and survival time of patients with cancers in advanced stage. VEGFR1 is frequently expressed in breast cancer, ovarian cancer, lung cancer, gastric cancer and other malignant tumors and their metastases. The VEGFR1/PD-L1 dual-targeting CAR-T will be investigated in cancer patients with serosal cavity metastases.

Conditions

Malignant Peritoneal Effusion; Malignant Ascites; Serous Cavity Metastatises

Keywords

CAR-T regional injection; Solid Tumors; Serosal Cavity metastases

Outcome Measures

Primary Outcomes (4)

• AEs will be recorded and evaluated by CTCAT 5.0.

  Safety

  28 days

• Recommended phase II dose (RP2D).

  Efficacy dose

  Approximately 18 months.

• Therapeutic efficacy will be evaluated according to RECIST1.1.

  Ant-tumor effects

  Approximately 18 months.

• Dose-limiting toxicity (DLT) will be assessed by CTCAE 5.0.

  Tolerability evaluation

  28 days

Secondary Outcomes (7)

• Objective Remission Rate (ORR).

  3 months

• Progression-Free Survival (PFS ).

  Approximately 18 months.

• Duration Of Control Rate (DCR).

  3 months

• Duration Of Response (DOR).

  Approximately 18 months.

• Overall-Survival (OS).

  Approximately 18 months.

Study Arms (1)

CAR-T cell therapy

EXPERIMENTAL

Dual-targeting VEGFR1 and PD-L1 CAR-T cells

Biological: Dual-targeting VEGFR1 and PD-L1 CAR-T cells

Interventions

Dual-targeting VEGFR1 and PD-L1 CAR-T cells BIOLOGICAL

In the dose escalation part, the dose levels will be escalated following a traditional escalation scheme for 3+3 design. In the dose expansion part, patients will be assigned to different groups based on pleural or peritoneal metastases condition.

CAR-T cell therapy

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, Age 18-65 years old; negative results of serum or urine pregnancy test within 48 hours before treatment are needed to provide for fertile women (or women who have undergone sterilization or at least 2 years after menopause can be regarded as infertile);
• Patients diagnosed as ovarian cancer, non-small cell lung cancer, breast cancer, gastric cancer, etc., accompanied by serous cavity metastasis, have received systemic standard treatment, and have clinical symptoms of serous cavity metastasis;
• The Eastern Cooperative Oncology Group (ECOG) performance status score is 0-2;
• Estimated life expectancy ≥ 3 months (according to investigator's judgement);
• Absolute neutrophil count ≥ 1.5×10\^9/L, platelet count ≥ 90×10\^9/L, absolute lymphocyte count ≥1×10\^8/L, hemoglobin ≥ 9.0 g/dL;
• Creatinine clearance rate ≥60 mL/min, Serum ALT/AST≤2.5 times of the normal level, and total bilirubin≤1.5 times of the normal level;
• Cardiac ejection fraction ≥50%, no pericardial effusion;
• No other serious diseases (autoimmune diseases or any immune deficiency disease or other disease in need of immunosuppressive therapy);
• Patients must stop chemotherapy and targeted therapy for at least 3 weeks before starting treatment;
• Patients must take reliable contraceptive measures before entering the trial, during the research process until 1 year after CAR-T infusion; reliable contraceptive measures will be determined by the main investigator or designated personnel;
• Voluntarily participate in the research, understand and sign the informed consent;
• The side effect of the last anti-tumor treatment was reduced to ≤1 grade, except for hair loss.

You may not qualify if:

• Had accepted any treatment of CAR-T therapy;
• Allergic to cytokines; uncontrolled activity infection;
• Acute or chronic (graft-versus-host disease) GVHD;
• Accompanied by other uncontrolled malignant tumors;
• Patient with hepatitis B or C active period, HIV infection ≥ the upper limit of the normal level;
• Other uncontrolled diseases in active period that hinder participation in the trial;
• Suffer from serious diseases such as coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis, cerebral hemorrhage, etc.;
• Patients with grade 2-3 hypertension or poorly controlled;
• History of mental illness that is difficult to control;
• Patients have used immunosuppressive agents for a long time after organ transplantation, except for recent or current inhaled corticosteroid therapy;
• The existing medical history or mental state history or laboratory abnormalities may increase the risk associated with participating in the study or the administration of the study drug from the point view of PI;
• Unstable pulmonary embolism, deep venous embolism or other major arterial/venous thromboembolic events occurred within 6 months before enrollment. If receiving anticoagulant therapy;
• Pregnant or nursing women, or plan to become pregnant during the treatment period or within 1 year after the treatment ends;
• Female subjects of childbearing age were reluctant to accept high-efficiency contraceptive measures during the treatment period or within 1 year after the treatment ends;
• Patient suffering from diseases that have signed written informed consent or comply with research procedures; or are unwilling or unable to comply with research requirements;

Sponsors & Collaborators

• Sichuan University: lead

Study Sites (1)

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

Related Publications (2)

• Cheema PK, Burkes RL. Overall survival should be the primary endpoint in clinical trials for advanced non-small-cell lung cancer. Curr Oncol. 2013 Apr;20(2):e150-60. doi: 10.3747/co.20.1226.

  PMID: 23559882 BACKGROUND

• Wagner DL, Fritsche E, Pulsipher MA, Ahmed N, Hamieh M, Hegde M, Ruella M, Savoldo B, Shah NN, Turtle CJ, Wayne AS, Abou-El-Enein M. Immunogenicity of CAR T cells in cancer therapy. Nat Rev Clin Oncol. 2021 Jun;18(6):379-393. doi: 10.1038/s41571-021-00476-2. Epub 2021 Feb 25.

  PMID: 33633361 BACKGROUND

Study Officials

• YongShen Wang, Prof.

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

XIA HE, Ph.D

CONTACT

18583365730; 18583365730@163.com

DAN LI, Ph.D

CONTACT

13880025826; lidan@wchscu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Institute of Drug Clinical Trial of West China Hospital

Study Record Dates

• First Submitted: May 7, 2022
• First Posted: July 28, 2022
• Study Start: November 28, 2023
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: November 29, 2023

Record last verified: 2023-11

Locations

CN (1)